Verification of chemical warfare agent exposure in human samples

AIM: This brief presentation provides an overview of methods that have been developed for the verification of human exposure to chemical warfare agents. METHODS: GC-MS detection of nerve agents (V- and G-type) has been carried out with respect to unreacted agents as well as enzyme-bound species and metabolites. METHODS involving direct SPE from plasma, fluoride-induced release of protein-bound nerve agents in plasma and analysis of their metabolites in plasma and urine have been developed. Exposure to blistering agents, i.e., sulfur mustard, has been verified by GC-MS detection of the unreacted agent in plasma and by LC- and GC-MS analysis of its metabolites in urine. RESULTS: After incorporation nerve agents quickly bind to proteins, e.g., acetylcholinesterase, butyrylcholinesterase or serum albumin, and only small parts remain freely circulating for a few hours (G-type) or up to 2 days (V-type). Concurrently they are converted to O-alkyl methylphosphonic acids by phosphotriesterases and/or simply by aqueous hydrolysis. As a re- sult, different biomarkers can be detected depending on the time passed between exposure and sampling. Unreacted V-type agents can be detected in plasma for 2 days, the O-alkyl methyl- phosphonic acids in plasma for about 2-4 days and in urine for up to 1 week. Fluoride-indu- ced release of protein-bound nerve agents can be carried out until 3 weeks post exposure. Unmetabolized sulfur mustard may be detected between 8 hours to 8 weeks in plasma, while no time frame has been reported for its metabolites in urine. CONCLUSION: A set of validated techniques detecting exposure to chemical warfare agents has been established. Further methods are needed to provide a clear picture of their biomarkers. Language: en